Medulloblastomas (MBs) originate in the cerebellum and have a propensity to disseminate throughout the central nervous system (1). Although aggressive multimodal therapy has improved the prognosis for children with MB, a significant proportion of patients are currently incurable (2). Moreover, survivors often suffer significant treatment-related morbidities, including neurocognitive deficits related to radiation therapy. New insights into the pathogenesis of these tumors are therefore sorely needed. Gene-based research has identified two subgroups of MBs, one associated with mutated genes within the sonic hedgehog pathway and the other associated with altered Wnt pathway genes (3, 4). Amplifications of MYC and OTX2 (5-7), mutations in TP53 (8), and a number of chromosomal alterations have also been identified in MBs. These discoveries have helped define the pathogenesis of MB and have improved our ability to identify patients who might benefit from therapies targeting these pathways. However, most MB patients do not have alterations in these genes and the compendium of genetic alterations causing MB is unknown.
There is a continuing need in the art to obtain improved tools for diagnosing, treating, and predicting the course of brain tumors; childhood tumors, and medulloblastomas.